1. Field of the Invention
The present invention relates to the production of nonhygroscopic alkaline earth salts of 4-hydroxybutyric acid suitable in the production of pharmaceutical preparations.
2. Brief Description of the Background of the Invention Including Prior Art
It is known that 4-hydroxy-butyric acid is liquid and a crystalline form can ony be obtained with difficulty. Also 4-hydroxybutyric acid is not available commercially in a pure composition. The sodium salts of the 4-hydroxybutyric acid are hygroscopic. The calcium salts known from British Pat. No. 922,029 of the 4-hydroxybutyric acid have been disclosed as being suitable for application only in liquid form in solution. A melting point for the calcium salt was not provided, presumably because it could not be determined based on the strong hygroscopicity. According to British Pat. No. 922,029 the hygroscopic calcium salt is obtained by reacting 4-butyrolactone with a solution of calciumhydroxide. This is a general method of operation, however the reaction is very violent and strongly exothermic, such that side reactions can occur resulting in final products which are difficult or not all suitable for crystallization. Presently completely unknown are magnesium salts of .gamma.-hydroxybutyric acid.
Therefor, up to now a general and wider therapeutic application was excluded for the 4-hydroxybutyric acid and its salts be it in the form of tablets, dragees and/or capsules. Based on the difficulties of production and handling of the 4-hydroxy-butyric acid and its salts, these are also very expensive.
It is further known that 4-hydroxybutyric acid has narcotic effects. It is successfully applied in medicine as an intravenously injectable anesthetic in the form of the sodium salt. The sodium salt, depending on the dose, generates a sleeping state from which the patient can be waked up.
However the free 4-hydroxybutyric acid as well as its sodium salt and the calcium salt taught in British Pat. No. 922,029 have not been applicable on a broad scale in pharmacy because of their strong hygroscopic action.
However, there is a large desire for these materials especially as sleeping agent and as a tranquilizer, since virtually all the known sleeping agents and tranquilizers such as barbiturates, amides, but also diazepams are associated with large side effects upon continuous application, but also directly associated with undesired aftereffects. In particular all present sleeping agents and tranquilizers interfere in an undesirable way with the metabolism of the nerves and this is also true for the plant derived agents such as those of valerian. Especially they are transformed into uncontrollable metabolites with obscure action and they frequently damage the liver irreversibly.
It is in fact known from the non-poisonous 4-hydroxybutyric acid that it acts as a sleeping drug (compare G. Kuschinsky, Taschenbuch der modernen Arzneibehandlung, 8th edition, 1980, page 328), however a handy oral application in the form of tablets, dragees or capsules of the compounds known in this respect has been impossible up to now because of the strong hygroscopicity of the known compounds. Even as solutions the known compounds were not exactly measurable as a dose, since hygroscopic materials always rapidly attract water, even upon weighing, such that in large scale production of pharmaceutical agents constant doses cannot be maintained.